{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:56:37Z","timestamp":1792306597924,"version":"4.4.0"},"reference-count":189,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>HIV-1\/AIDS remains a global public health problem. The world health organization (WHO) reported at the end of 2019 that 38 million people were living with HIV-1 worldwide, of which only 67% were accessing antiretroviral therapy (ART). Despite great success in the clinical management of HIV-1 infection, ART does not eliminate the virus from the host genome. Instead, HIV-1 remains latent as a viral reservoir in any tissue containing resting memory CD4+ T cells. The elimination of these residual proviruses that can reseed full-blown infection upon treatment interruption remains the major barrier towards curing HIV-1. Novel approaches have recently been developed to excise or disrupt the virus from the host cells (e.g., gene editing with the CRISPR-Cas system) to permanently shut off transcription of the virus (block-and-lock and RNA interference strategies), or to reactivate the virus from cell reservoirs so that it can be eliminated by the immune system or cytopathic effects (shock-and-kill strategy). Here, we will review each of these approaches, with the major focus placed on the block-and-lock strategy.<\/jats:p>","DOI":"10.3390\/v12121443","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T21:11:02Z","timestamp":1608066662000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Block-And-Lock: New Horizons for a Cure for HIV-1"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-0670","authenticated-orcid":false,"given":"Ines","family":"Moranguinho","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana T.","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020). HIV-AIDS, WHO. Fact sheets."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hamlyn, E., Ewings, F.M., Porter, K., Cooper, D.A., Tambussi, G., Schechter, M., Pedersen, C., Okulicz, J.F., McClure, M., and Babiker, A. (2012). Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043754"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.coviro.2016.03.004","article-title":"Current status and prospects of HIV treatment","volume":"18","author":"Cihlar","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","article-title":"Targeting the Latent Reservoir for HIV-1","volume":"48","author":"Sengupta","year":"2018","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e003371","DOI":"10.1161\/JAHA.116.003371","article-title":"Inflammatory markers associated with subclinical coronary artery disease: The multicenter AIDS cohort study","volume":"5","author":"Bahrami","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1096\/fj.201600368RR","article-title":"Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-\u03baB in endothelial cells","volume":"30","author":"Tang","year":"2016","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/infdis\/jis545","article-title":"Biomarkers of Microbial Translocation and Macrophage Activation: Association With Progression of Subclinical Atherosclerosis in HIV-1 Infection","volume":"206","author":"Kelesidis","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.meegid.2016.08.031","article-title":"HIV-1 drug resistance and resistance testing","volume":"46","author":"Clutter","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s40265-020-01284-1","article-title":"Advances in Long-Acting Agents for the Treatment of HIV Infection","volume":"80","author":"Rana","year":"2020","journal-title":"Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Meyers, K., Rodriguez, K., Moeller, R.W., Gratch, I., Markowitz, M., and Halkitis, P.N. (2014). High interest in a long-acting injectable formulation of pre-exposure prophylaxis for HIV in young men who have sex with men in NYC: A P18 cohort substudy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114700"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1007\/s00018-019-03156-8","article-title":"Strategies to eradicate HIV from infected patients: Elimination of latent provirus reservoirs","volume":"76","author":"Sadowski","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11904-013-0197-1","article-title":"Practical considerations in gene therapy for HIV cure","volume":"11","author":"Stan","year":"2014","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1056\/NEJMoa0802905","article-title":"Long-term control of HIV by CCR5 delta32\/delta32 stem-cell transplantation","volume":"360","author":"Hutter","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41586-019-1027-4","article-title":"HIV-1 remission following CCR5\u039432\/\u039432 haematopoietic stem-cell transplantation","volume":"568","author":"Gupta","year":"2019","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/COH.0b013e328344f35e","article-title":"Epidemiology and clinical characteristics of elite controllers","volume":"6","author":"Okulicz","year":"2011","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41586-020-2651-8","article-title":"Distinct viral reservoirs in individuals with spontaneous control of HIV-1","volume":"585","author":"Jiang","year":"2020","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11904-016-0296-x","article-title":"Post-Treatment Controllers: Role in HIV \u201cCure\u201d Research","volume":"13","author":"Cockerham","year":"2016","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev-med-092112-152941","article-title":"Understanding HIV Latency: The Road to an HIV Cure","volume":"66","author":"Dahabieh","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.immuni.2017.09.014","article-title":"Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection","volume":"47","author":"Shan","year":"2017","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e02225-17","DOI":"10.1128\/JVI.02225-17","article-title":"The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed","volume":"92","author":"Rezaei","year":"2018","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jtbi.2009.06.011","article-title":"Modeling HIV persistence, the latent reservoir, and viral blips","volume":"260","author":"Rong","year":"2009","journal-title":"J. Theor. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4049\/jimmunol.1600343","article-title":"The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence","volume":"197","author":"Murray","year":"2016","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/COH.0000000000000122","article-title":"How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?","volume":"10","author":"Ananworanich","year":"2015","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"eaau0528","DOI":"10.1126\/scitranslmed.aau0528","article-title":"Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection","volume":"11","author":"Ndhlovu","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/8394","article-title":"Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy","volume":"5","author":"Finzi","year":"1999","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"Ho","year":"2013","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A quantitative approach for measuring the reservoir of latent HIV-1 proviruses","volume":"566","author":"Bruner","year":"2019","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1172\/JCI80567","article-title":"Measuring the latent reservoir in vivo","volume":"126","author":"Massanella","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Eriksson, S., Graf, E.H., Dahl, V., Strain, M.C., Yukl, S.A., Lysenko, E.S., Bosch, R.J., Lai, J., Chioma, S., and Emad, F. (2013). Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003174"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/COH.0000000000000438","article-title":"HIV integration sites and implications for maintenance of the reservoir","volume":"13","author":"Symons","year":"2018","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.antiviral.2019.03.008","article-title":"HIV \u201cshock and kill\u201d therapy: In need of revision","volume":"166","author":"Abner","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(02)00864-4","article-title":"HIV-1 integration in the human genome favors active genes and local hotspots","volume":"110","author":"Shinn","year":"2002","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1089\/aid.2018.0118","article-title":"Barriers for HIV Cure: The Latent Reservoir","volume":"34","year":"2018","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9148","DOI":"10.1128\/JVI.01297-13","article-title":"High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4+ T Cells in Virally Suppressed Subjects","volume":"87","author":"Vandergeeten","year":"2013","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/j.celrep.2020.01.071","article-title":"CD32+CD4+ T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency","volume":"30","author":"Darcis","year":"2020","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/COH.0000000000000230","article-title":"Residual inflammation and viral reservoirs: Alliance against an HIV cure","volume":"11","author":"Massanella","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12985-019-1276-8","article-title":"The forces driving clonal expansion of the HIV-1 latent reservoir","volume":"17","author":"Liu","year":"2020","journal-title":"Virol. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nm.1972","article-title":"HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation","volume":"15","author":"Chomont","year":"2009","journal-title":"Nat. Med."},{"key":"ref_39","first-page":"1","article-title":"HIV-1 transcription and latency: An update","volume":"10","author":"Bouchat","year":"2013","journal-title":"Retrovirology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/bs.ircmb.2017.07.011","article-title":"Transcription: Insights From the HIV-1 Promoter","volume":"335","author":"Ne","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.coviro.2019.07.011","article-title":"Targeting HIV-1 proviral transcription","volume":"38","author":"Olson","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2017.00080","article-title":"HIV-1 tat and viral latency: What we can learn from naturally occurring sequence variations","volume":"8","author":"Kamori","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1126\/science.2981427","article-title":"Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat","volume":"227","author":"Sodroski","year":"1985","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/330489a0","article-title":"Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product","volume":"330","author":"Kao","year":"1987","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0092-8674(89)90289-4","article-title":"Tat trans-activates the human immunodeficiency virus through a nascent RNA target","volume":"59","author":"Berkhout","year":"1989","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/1570162052772924","article-title":"HIV-1 TAR RNA: The Target of Molecular Interactions Between the Virus and its Host","volume":"3","author":"Bannwarth","year":"2005","journal-title":"Curr. HIV Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12951","DOI":"10.1074\/jbc.M006130200","article-title":"DSIF and NELF Interact with RNA Polymerase II Elongation Complex and HIV-1 Tat Stimulates P-TEFb-mediated Phosphorylation of RNA Polymerase II and DSIF during Transcription Elongation","volume":"276","author":"Ping","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1128\/MCB.20.8.2629-2634.2000","article-title":"P-TEFb, a Cyclin-Dependent Kinase Controlling Elongation by RNA Polymerase II","volume":"20","author":"Price","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S1097-2765(01)00314-8","article-title":"NF-\u03baB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II","volume":"8","author":"Barboric","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.molcel.2005.06.029","article-title":"Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4","volume":"19","author":"Yang","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"29713","DOI":"10.1074\/jbc.M110.125997","article-title":"P-TEFb Kinase Complex Phosphorylates Histone H1 to Regulate Expression of Cellular and HIV-1 Genes","volume":"285","author":"Cao","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/21541264.2017.1281864","article-title":"P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II","volume":"9","author":"Li","year":"2018","journal-title":"Transcription"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1006\/jmbi.1999.3060","article-title":"Tackling tat","volume":"293","author":"Karn","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0092-8674(00)80939-3","article-title":"A Novel CDK9-Associated C-Type Cyclin Interacts Directly with HIV-1 Tat and Mediates Its High-Affinity, Loop-Specific Binding to TAR RNA","volume":"92","author":"Wei","year":"1998","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1742-4690-2-69","article-title":"Tat gets the \u201cGreen\u201d light on transcription initiation","volume":"2","author":"Brady","year":"2005","journal-title":"Retrovirology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1002\/j.1460-2075.1993.tb05994.x","article-title":"Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation","volume":"12","author":"Verdin","year":"1993","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1128\/jvi.65.12.6790-6799.1991","article-title":"DNase I-hypersensitive sites are associated with both long terminal repeats and with the intragenic enhancer of integrated human immunodeficiency virus type 1","volume":"65","author":"Verdin","year":"1991","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19916","DOI":"10.1016\/S0021-9258(17)32107-5","article-title":"Protein-DNA interactions within DNase I-hypersensitive sites located downstream of the HIV-1 promoter","volume":"269","author":"Verdin","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1038\/sj.emboj.7601074","article-title":"Requirement for SWI\/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter","volume":"25","author":"Kiernan","year":"2006","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature08911","article-title":"Chromatin remodelling during development","volume":"463","author":"Ho","year":"2010","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pbio.1001206","article-title":"Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency","volume":"9","author":"Rafati","year":"2011","journal-title":"PLoS Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.virol.2010.06.009","article-title":"Transcription through the HIV-1 nucleosomes: Effects of the PBAF complex in Tat activated transcription","volume":"405","author":"Easley","year":"2010","journal-title":"Virology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jmb.2014.07.022","article-title":"Regulation of HIV-1 Latency by Chromatin Structure and Nuclear Architecture","volume":"427","author":"Lusic","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1128\/MCB.22.9.2965-2973.2002","article-title":"Counterregulation of Chromatin Deacetylation and Histone Deacetylase Occupancy at the Integrated Promoter of Human Immunodeficiency Virus Type 1 (HIV-1) by the HIV-1 Repressor YY1 and HIV-1 Activator Tat","volume":"22","author":"He","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1038\/sj.emboj.7601928","article-title":"CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency","volume":"26","author":"Tyagi","year":"2007","journal-title":"EMBO J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1128\/JVI.74.15.6790-6799.2000","article-title":"The Human Factors YY1 and LSF Repress the Human Immunodeficiency Virus Type 1 Long Terminal Repeat via Recruitment of Histone Deacetylase 1","volume":"74","author":"Coull","year":"2000","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/sj.emboj.7601517","article-title":"Suv39H1 and HP1\u03b3 are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency","volume":"26","author":"Basyuk","year":"2007","journal-title":"EMBO J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16538","DOI":"10.1074\/jbc.M110.103531","article-title":"Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294","volume":"285","author":"Imai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/j.1460-2075.1990.tb08222.x","article-title":"Inactivation of the HIV LTR by DNA CpG methylation: Evidence for a role in latency","volume":"9","author":"Bednarik","year":"1990","journal-title":"EMBO J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Blazkova, J., Trejbalova, K., Gondois-Rey, F., Halfon, P., Philibert, P., Guiguen, A., Verdin, E., Olive, D., Van Lint, C., and Hejnar, J. (2009). CpG methylation controls reactivation of HIV from latency. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000554"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ymeth.2010.05.009","article-title":"In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus","volume":"53","author":"Kauder","year":"2011","journal-title":"Methods"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"117","DOI":"10.15252\/emmm.201505557","article-title":"Sequential treatment with 5-aza-2\u2032-deoxycytidine and deacetylase inhibitors reactivates HIV-1","volume":"8","author":"Bouchat","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5390","DOI":"10.1128\/JVI.00040-12","article-title":"Paucity of HIV DNA Methylation in Latently Infected, Resting CD4+ T Cells from Infected Individuals Receiving Antiretroviral Therapy","volume":"86","author":"Blazkova","year":"2012","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13081","DOI":"10.1128\/JVI.01741-12","article-title":"Long-Term Nonprogressor and Elite Controller Patients Who Control Viremia Have a Higher Percentage of Methylation in Their HIV-1 Proviral Promoters than Aviremic Patients Receiving Highly Active Antiretroviral Therapy","volume":"86","author":"Palacios","year":"2012","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1128\/JVI.01316-08","article-title":"Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus Transcription through Phosphorylation of CDK9 at Threonine 29","volume":"83","author":"Zhou","year":"2009","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13690","DOI":"10.1073\/pnas.0705053104","article-title":"Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription","volume":"104","author":"Bisgrove","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.molcel.2005.06.027","article-title":"The Bromodomain Protein Brd4 Is a Positive Regulatory Component of P-TEFb and Stimulates RNA Polymerase II-Dependent Transcription","volume":"19","author":"Jang","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.molcel.2017.07.025","article-title":"The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI\/SNF Chromatin-Remodeling Complexes","volume":"67","author":"Conrad","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"13519","DOI":"10.1073\/pnas.95.23.13519","article-title":"HIV-1 Tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter","volume":"95","author":"Marzio","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0960-9822(00)80120-7","article-title":"Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity","volume":"9","author":"Ott","year":"1999","journal-title":"Curr. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/viro.2000.0593","article-title":"Acetylation of HIV-1 Tat by CBP\/P300 Increases Transcription of Integrated HIV-1 Genome and Enhances Binding to Core Histones","volume":"277","author":"Deng","year":"2000","journal-title":"Virology"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Delannoy, A., Poirier, M., and Bell, B. (2019). Cat and Mouse: HIV Transcription in Latency, Immune Evasion and Cure\/Remission Strategies. Viruses, 11.","DOI":"10.3390\/v11030269"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.chom.2017.12.004","article-title":"Getting the \u201cKill\u201d into \u201cShock and Kill\u201d: Strategies to Eliminate Latent HIV","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/aid.2018.0153","article-title":"Current Strategies for Elimination of HIV-1 Latent Reservoirs Using Chemical Compounds Targeting Host and Viral Factors","volume":"35","author":"Jean","year":"2019","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1146\/annurev-med-011514-023043","article-title":"Progress Toward HIV Eradication: Case Reports, Current Efforts, and the Challenges Associated with Cure","volume":"67","author":"Martin","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/med.21638","article-title":"Diversity of small molecule HIV-1 latency reversing agents identified in low- and high-throughput small molecule screens","volume":"40","author":"Hashemi","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"102667","DOI":"10.1016\/j.ebiom.2020.102667","article-title":"Pathways towards human immunodeficiency virus elimination","volume":"53","author":"Dash","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature11286","article-title":"Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy","volume":"487","author":"Archin","year":"2012","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Elliott, J.H., Wightman, F., Solomon, A., Ghneim, K., Ahlers, J., Cameron, M.J., Smith, M.Z., Spelman, T., McMahon, J., and Velayudham, P. (2014). Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004473"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1172\/JCI92684","article-title":"Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency","volume":"127","author":"Archin","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.molmed.2015.11.004","article-title":"HIV-1 Eradication: Early Trials (and Tribulations)","volume":"22","author":"Spivak","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2352-3018(14)70014-1","article-title":"Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: A phase 1\/2, single group, clinical trial","volume":"1","author":"Rasmussen","year":"2014","journal-title":"Lancet HIV"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"S\u00f8gaard, O.S., Graversen, M.E., Leth, S., Olesen, R., Brinkmann, C.R., Nissen, S.K., Kjaer, A.S., Schleimann, M.H., Denton, P.W., and Hey-Cunningham, W.J. (2015). The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLOS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005142"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1089\/aid.2014.0199","article-title":"Targeting NF-\u03baB Signaling with Protein Kinase C Agonists As an Emerging Strategy for Combating HIV Latency","volume":"31","author":"Jiang","year":"2015","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nm.3489","article-title":"New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo","volume":"20","author":"Bullen","year":"2014","journal-title":"Nat. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.1128\/AAC.01077-15","article-title":"Ex Vivo Bioactivity and HIV-1 Latency Reversal by Ingenol Dibenzoate and Panobinostat in Resting CD4 + T Cells from Aviremic Patients","volume":"59","author":"Spivak","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Jiang, G., Mendes, E.A., Kaiser, P., Wong, D.P., Tang, Y., Cai, I., Fenton, A., Melcher, G.P., Hildreth, J.E.K., and Thompson, G.R. (2015). Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation. PLOS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005066"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1172\/JCI80142","article-title":"Ex vivo analysis identifies effective HIV-1 latency\u2013reversing drug combinations","volume":"125","author":"Laird","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"160","DOI":"10.15252\/emmm.201708193","article-title":"Compounds producing an effective combinatorial regimen for disruption of HIV-1 latency","volume":"10","author":"Hashemi","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.3389\/fimmu.2018.01452","article-title":"Diverse impacts of HIV latency-reversing agents on CD8+ T-cell function: Implications for HIV cure","volume":"9","author":"Clutton","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e463","DOI":"10.1016\/S2352-3018(16)30055-8","article-title":"Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): A single-arm, phase 1B\/2A trial","volume":"3","author":"Leth","year":"2016","journal-title":"Lancet HIV"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-med-052716-031710","article-title":"Novel Latency Reversal Agents for HIV-1 Cure","volume":"69","author":"Spivak","year":"2018","journal-title":"Annu. Rev. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.03162","article-title":"Antigen Production After Latency Reversal and Expression of Inhibitory Receptors in CD8+ T Cells Limit the Killing of HIV-1 Reactivated Cells","volume":"9","author":"Ruiz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Grau-Exp\u00f3sito, J., Luque-Ballesteros, L., Navarro, J., Curran, A., Burgos, J., Ribera, E., Torrella, A., Planas, B., Bad\u00eda, R., and Martin-Castillo, M. (2019). Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations. PLOS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007991"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.tim.2015.11.003","article-title":"Reversal of Latency as Part of a Cure for HIV-1","volume":"24","author":"Rasmussen","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/QAD.0000000000001267","article-title":"Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques","volume":"31","author":"Gama","year":"2017","journal-title":"AIDS"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.celrep.2019.10.101","article-title":"Latency-Reversing Agents Induce Differential Responses in Distinct Memory CD4 T Cell Subsets in Individuals on Antiretroviral Therapy","volume":"29","author":"Pardons","year":"2019","journal-title":"Cell Rep."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Liu, C., Ma, X., Liu, B., Chen, C., and Zhang, H. (2015). HIV-1 functional cure: Will the dream come true?. BMC Med., 13.","DOI":"10.1186\/s12916-015-0517-y"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.it.2016.12.003","article-title":"HIV Latency: Should We Shock or Lock?","volume":"38","author":"Darcis","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Rands, C.M., Meader, S., Ponting, C.P., and Lunter, G. (2014). 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004525"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.celrep.2017.09.080","article-title":"In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a \u201cBlock-and-Lock\u201d Strategy for HIV-1 Treatment","volume":"21","author":"Kessing","year":"2017","journal-title":"Cell Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF00125123","article-title":"A region of basic amino-acid cluster in HIV-1 Tat protein is essential forTrans-acting activity and nucleolar localization","volume":"3","author":"Endo","year":"1989","journal-title":"Virus Genes"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.cell.2015.02.009","article-title":"A Hardwired HIV Latency Program","volume":"160","author":"Razooky","year":"2015","journal-title":"Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.2174\/092986706776872989","article-title":"Inhibitors of HIV-1 Tat-Mediated Transactivation","volume":"13","author":"Richter","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chom.2012.05.016","article-title":"An Analog of the Natural Steroidal Alkaloid Cortistatin A Potently Suppresses Tat-Dependent HIV Transcription","volume":"12","author":"Mousseau","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"8280","DOI":"10.1096\/fj.201801165R","article-title":"The Tat inhibitor didehydro-cortistatin A suppresses SIV replication and reactivation","volume":"33","author":"Mediouni","year":"2019","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.02662-18","article-title":"Didehydro-Cortistatin A Inhibits HIV-1 by Specifically Binding to the Unstructured Basic Region of Tat","volume":"10","author":"Mediouni","year":"2019","journal-title":"MBio"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e00465","DOI":"10.1128\/mBio.00465-15","article-title":"The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency","volume":"6","author":"Mousseau","year":"2015","journal-title":"MBio"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13072-019-0267-8","article-title":"Tat inhibition by didehydro-Cortistatin A promotes heterochromatin formation at the HIV-1 long terminal repeat","volume":"12","author":"Li","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2174\/1570162X13666150121111548","article-title":"Didehydro-Cortistatin A Inhibits HIV-1 Tat Mediated Neuroinflammation and Prevents Potentiation of Cocaine Reward in Tat Transgenic Mice","volume":"13","author":"Mediouni","year":"2015","journal-title":"Curr. HIV Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1046\/j.1471-4159.2002.01212.x","article-title":"Human immunodeficiency virus-1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function","volume":"83","author":"Maragos","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s00296-011-1841-y","article-title":"A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: Mechanism, efficacy, and safety","volume":"31","author":"Bao","year":"2011","journal-title":"Rheumatol. Int."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12977-014-0088-6","article-title":"Triptolide inhibits human immunodeficiency virus type 1 replication by promoting proteasomal degradation of Tat protein","volume":"11","author":"Wan","year":"2014","journal-title":"Retrovirology"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Wang, Y., Lu, J., He, L., and Yu, Q. (2011). Triptolide (TPL) Inhibits Global Transcription by Inducing Proteasome-Dependent Degradation of RNA Polymerase II (Pol II). PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023993"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nchembio.522","article-title":"XPB, a subunit of TFIIH, is a target of the natural product triptolide","volume":"7","author":"Titov","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.antiviral.2017.08.013","article-title":"Screening of an FDA-approved compound library identifies levosimendan as a novel anti-HIV-1 agent that inhibits viral transcription","volume":"146","author":"Hayashi","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2147\/vhrm.2006.2.4.389","article-title":"A review of levosimendan in the treatment of heart failure","volume":"2","author":"Kasikcioglu","year":"2006","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.chembiol.2013.12.014","article-title":"A Small Molecule Screen Identifies an Inhibitor of DNA Repair Inducing the Degradation of TFIIH and the Chemosensitization of Tumor Cells to Platinum","volume":"21","author":"Alekseev","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"10972","DOI":"10.1128\/JVI.01722-16","article-title":"Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells","volume":"90","author":"Lacombe","year":"2016","journal-title":"J. Virol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"27297","DOI":"10.1074\/jbc.M115.652339","article-title":"FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency","volume":"290","author":"Huang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"95ra74","DOI":"10.1126\/scitranslmed.3002530","article-title":"Curaxins: Anticancer Compounds That Simultaneously Suppress NF- B and Activate p53 by Targeting FACT","volume":"3","author":"Gasparian","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.3389\/fmicb.2017.02007","article-title":"Curaxin CBL0100 Blocks HIV-1 Replication and Reactivation through Inhibition of Viral Transcriptional Elongation","volume":"8","author":"Jean","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00018-009-0163-7","article-title":"Key factors in mTOR regulation","volume":"67","author":"Bai","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbapap.2009.12.001","article-title":"Dissecting the role of mTOR: Lessons from mTOR inhibitors","volume":"1804","author":"Dowling","year":"2010","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"10411","DOI":"10.1073\/pnas.1834278100","article-title":"Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV -chemokines: An approach to suppress R5 strains of HIV-1","volume":"100","author":"Heredia","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"9412","DOI":"10.1073\/pnas.1511144112","article-title":"Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice","volume":"112","author":"Heredia","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri3198","article-title":"Regulation and function of mTOR signalling in T cell fate decisions","volume":"12","author":"Chi","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1600-065X.2012.01094.x","article-title":"Dynamic roles for NF-\u03baB in HTLV-I and HIV-1 retroviral pathogenesis","volume":"246","author":"Chan","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.chom.2016.11.001","article-title":"The mTOR Complex Controls HIV Latency","volume":"20","author":"Besnard","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41426-018-0139-5","article-title":"TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway","volume":"7","author":"Jin","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1172\/JCI120633","article-title":"Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV","volume":"129","author":"Niu","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"39314","DOI":"10.1074\/jbc.M110.155275","article-title":"Gyrase B Inhibitor Impairs HIV-1 Replication by Targeting Hsp90 and the Capsid Protein","volume":"285","author":"Vozzolo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"24581","DOI":"10.1074\/jbc.M111.248021","article-title":"Impaired infectivity of ritonavir-resistant HIV is rescued by heat shock protein 90AB1","volume":"286","author":"Joshi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"28896","DOI":"10.1038\/srep28896","article-title":"Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"E1528","DOI":"10.1073\/pnas.1320178111","article-title":"Heat shock protein 90 controls HIV-1 reactivation from latency","volume":"111","author":"Anderson","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"10332","DOI":"10.1074\/jbc.M116.717538","article-title":"Inhibition of Heat Shock Protein 90 Prevents HIV Rebound","volume":"291","author":"Joshi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Mizukoshi, E., and Kaneko, S. (2019). Telomerase-Targeted Cancer Immunotherapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081823"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.bbrc.2016.01.160","article-title":"A telomerase-derived peptide regulates reactive oxygen species and hepatitis C virus RNA replication in HCV-infected cells via heat shock protein 90","volume":"471","author":"Lee","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA Targets. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020363"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/nm1639","article-title":"Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes","volume":"13","author":"Huang","year":"2007","journal-title":"Nat. Med."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Sung, T.-L., and Rice, A.P. (2009). miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000263"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1128\/JVI.05065-11","article-title":"Regulation of Cyclin T1 and HIV-1 Replication by MicroRNAs in Resting CD4+ T Lymphocytes","volume":"86","author":"Chiang","year":"2012","journal-title":"J. Virol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00705-016-2755-5","article-title":"Expression of HIV-encoded microRNA-TAR and its inhibitory effect on viral replication in human primary macrophages","volume":"161","author":"Li","year":"2016","journal-title":"Arch. Virol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1128\/JVI.78.13.7079-7088.2004","article-title":"Antisense-Mediated Inhibition of Human Immunodeficiency Virus (HIV) Replication by Use of an HIV Type 1-Based Vector Results in Severely Attenuated Mutants Incapable of Developing Resistance","volume":"78","author":"Lu","year":"2004","journal-title":"J. Virol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2741\/1782","article-title":"HIV-1 inactivation by nucleic acid aptamers","volume":"11","author":"Held","year":"2006","journal-title":"Front. Biosci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.3390\/ph6121507","article-title":"Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases","volume":"6","author":"Shum","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/mt.2008.92","article-title":"Novel Dual Inhibitory Function Aptamer\u2013siRNA Delivery System for HIV-1 Therapy","volume":"16","author":"Zhou","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e228","DOI":"10.1038\/mtna.2015.1","article-title":"High-affinity RNA Aptamers Against the HIV-1 Protease Inhibit Both In Vitro Protease Activity and Late Events of Viral Replication","volume":"4","author":"Duclair","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.chembiol.2015.01.005","article-title":"Cell-Specific RNA Aptamer against Human CCR5 Specifically Targets HIV-1 Susceptible Cells and Inhibits HIV-1 Infectivity","volume":"22","author":"Zhou","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-4939-2432-5_11","article-title":"Aptamer\u2013siRNA Chimeras for HIV","volume":"848","author":"Takahashi","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nbt0502-500","article-title":"Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells","volume":"20","author":"Lee","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"9225","DOI":"10.1128\/JVI.76.18.9225-9231.2002","article-title":"Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference","volume":"76","author":"Coburn","year":"2002","journal-title":"J. Virol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nm725","article-title":"siRNA-directed inhibition of HIV-1 infection","volume":"8","author":"Novina","year":"2002","journal-title":"Nat. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/sj.gt.3302786","article-title":"Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA","volume":"13","author":"Konstantinova","year":"2006","journal-title":"Gene Ther."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nature00896","article-title":"Modulation of HIV-1 replication by RNA interference","volume":"418","author":"Jacque","year":"2002","journal-title":"Nature"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1093\/nar\/gki220","article-title":"HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome","volume":"33","author":"Westerhout","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1128\/JVI.78.5.2601-2605.2004","article-title":"Human Immunodeficiency Virus Type 1 Escapes from RNA Interference-Mediated Inhibition","volume":"78","author":"Das","year":"2004","journal-title":"J. Virol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1742-4690-4-80","article-title":"Optimal design and validation of antiviral siRNA for targeting HIV-1","volume":"4","author":"Naito","year":"2007","journal-title":"Retrovirology"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Ringpis, G.-E.E., Shimizu, S., Arokium, H., Camba-Col\u00f3n, J., Carroll, M.V., Cortado, R., Xie, Y., Kim, P.Y., Sahakyan, A., and Lowe, E.L. (2012). Engineering HIV-1-Resistant T-Cells from Short-Hairpin RNA-Expressing Hematopoietic Stem\/Progenitor Cells in Humanized BLT Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053492"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2007.03.005","article-title":"RNAi therapeutics: Principles, prospects and challenges","volume":"59","author":"Aagaard","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_171","first-page":"1559","article-title":"Genome editing: A perspective on the application of CRISPR\/Cas9 to study human diseases (Review)","volume":"43","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"eaba7365","DOI":"10.1126\/science.aba7365","article-title":"CRISPR-engineered T cells in patients with refractory cancer","volume":"367","author":"Stadtmauer","year":"2020","journal-title":"Science"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/34814","article-title":"CCR5 is characteristic of Th1 lymphocytes","volume":"391","author":"Loetscher","year":"1998","journal-title":"Nature"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40169-020-0268-z","article-title":"The clinical potential of gene editing as a tool to engineer cell-based therapeutics","volume":"9","author":"Fruhwirth","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"22555","DOI":"10.1038\/srep22555","article-title":"Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR\/Cas9 Gene Editing","volume":"6","author":"Kaminski","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/gt.2016.41","article-title":"Excision of HIV-1 DNA by gene editing: A proof-of-concept in vivo study","volume":"23","author":"Kaminski","year":"2016","journal-title":"Gene Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1038\/srep02510","article-title":"Harnessing the CRISPR\/Cas9 system to disrupt latent HIV-1 provirus","volume":"3","author":"Ebina","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.celrep.2016.03.042","article-title":"CRISPR\/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape","volume":"15","author":"Wang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1097\/QAD.0000000000001079","article-title":"Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS","volume":"30","author":"Yin","year":"2016","journal-title":"AIDS"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex Genome Engineering Using CRISPR\/Cas Systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1056\/NEJMoa1817426","article-title":"CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia","volume":"381","author":"Xu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1056\/NEJMc1405805","article-title":"Shift of HIV Tropism in Stem-Cell Transplantation with CCR5 Delta32 Mutation","volume":"371","author":"Kordelas","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.15252\/embr.201541337","article-title":"No time to waste\u2014The ethical challenges created by CRISPR","volume":"16","author":"Caplan","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11569-016-0259-0","article-title":"CRISPR\/Cas9 genome editing\u2014New and old ethical issues arising from a revolutionary technology","volume":"10","author":"Baumann","year":"2016","journal-title":"Nanoethics"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1126\/science.362.6418.978","article-title":"Shock greets claim of CRISPR-edited babies","volume":"362","author":"Normile","year":"2018","journal-title":"Science"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/imr.12065","article-title":"Immune activation and HIV persistence: Implications for curative approaches to HIV infection","volume":"254","author":"Klatt","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.cell.2015.02.017","article-title":"An Evolutionary Role for HIV Latency in Enhancing Viral Transmission","volume":"160","author":"Rouzine","year":"2015","journal-title":"Cell"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"9529","DOI":"10.1128\/JVI.00919-14","article-title":"Unfixed Endogenous Retroviral Insertions in the Human Population","volume":"88","author":"Marchi","year":"2014","journal-title":"J. Virol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"REVIEWS1017","DOI":"10.1186\/gb-2001-2-6-reviews1017","article-title":"Endogenous retroviruses in the human genome sequence","volume":"2","author":"Griffiths","year":"2001","journal-title":"Genome Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:45:29Z","timestamp":1760179529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":189,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["v12121443"],"URL":"https:\/\/doi.org\/10.3390\/v12121443","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,15]]}}}